Th22 cells as well as Th17 cells expand differentially in patients with early-stage and late-stage myelodysplastic syndrome.
Th22 cells as well as Th17 cells expand differentially in patients with early-stage and late-stage myelodysplastic syndrome.
复制标题
早期和晚期骨髓增生异常综合征患者中 Th22 细胞和 Th17 细胞的扩增存在差异
DOI：
10.1371/journal.pone.0051339
复制
发表时间：
2012
期刊：
影响因子：
3.7
通讯作者：
Hou M
中科院分区：
文献类型：
--
作者：
Shao LL;Zhang L;Hou Y;Yu S;Liu XG;Huang XY;Sun YX;Tian T;He N;Ma DX;Peng J;Hou M
免疫机制在骨髓增生异常综合征（MDS）的进展中越来越受到重视。早期MDS（E-MDS）的特征在于自身免疫介导的骨髓抑制，而晚期MDS（L-MDS）涉及免疫逃避，使发育不良细胞具有发展成急性髓性白血病的生长潜力。辅助性T细胞（Th）22参与炎症性自身免疫和肿瘤发生的发病机制。Th 22细胞在E-MDS和L-MDS的病理生理学中的作用仍然不确定。我们研究了37例MDS患者（E-MDS，n = 17; L-MDS，n = 20）和20名健康对照以表征其外周血（PB），以及25例MDS患者和10名健康对照以表征其骨髓（BM）。 采用流式细胞术检测E-MDS、L-MDS患者及正常对照组外周血白细胞介素22（IL-22）、IL-17及干扰素γ（IFN-γ）的表达。采用实时荧光定量聚合酶链反应（PCR）检测外周血单个核细胞（PBMC）中RAR相关孤儿受体C（RORC）、IL-6、肿瘤坏死因子α（TNF-α）和IL-23的mRNA表达水平。采用酶联免疫吸附法检测外周血和骨髓中IL-22和IL-17的水平。与健康对照组和L-MDS相比，E-MDS患者外周血Th 17细胞显著升高，并与外周血Th 22细胞相关。与E-MDS相比，L-MDS患者外周血Th 22细胞扩增、IL-6、TNF-α mRNA表达水平显著增高，RORC mRNA表达水平显著降低。E-MDS、L-MDS和对照组IL-23 mRNA表达或血浆IL-22、IL-17水平无统计学差异。结果表明，L-MDS患者外周血Th 22细胞比例增高，IL-6和TNF-α mRNA表达水平增高，提示Th 22细胞沿着Th 17细胞参与了MDS的动态免疫应答。
Immunological mechanisms are increasingly recognized in the progression of myelodysplastic syndrome (MDS). Early-stage MDS (E-MDS) is characterized by autoimmune-mediated myelosuppression whereas late-stage MDS (L-MDS) involves immune evasion, giving dysplastic cells growth potential to progress into acute myeloid leukemia. T-helper (Th) 22 is involved in the pathogenesis of inflammatory autoimmunity and tumorigenesis. The roles of Th22 cells in the pathophysiology of E-MDS and L-MDS remain unsettled. We studied 37 MDS patients (E-MDS, n = 17; L-MDS, n = 20) and 20 healthy controls to characterize their peripheral blood (PB), as well as 25 MDS patients and 10 healthy controls to characterize their bone marrow(BM). The expression of Interleukin-22 (IL-22), IL-17 or interferon gamma (IFN-γ) was examined in E-MDS, L-MDS patients and controls by flow cytometry. The mRNA expression levels of RAR-related orphan receptor C (RORC), IL-6, tumor necrosis factor alpha (TNF-α) and IL-23 in peripheral blood mononuclear cells (PBMCs) were determined by real-time quantitative polymerase chain reaction. The levels of IL-22 and IL-17 both in PB and BM plasma were examined by enzyme-linked immunosorbent assay. In E-MDS, peripheral Th17 cells were significantly elevated and correlated with peripheral Th22 cells compared with healthy controls and L-MDS. Significantly higher levels of peripheral Th22 expansion, mRNA expression of IL-6, TNF-α and lower level of RORC mRNA expression were observed in L-MDS compared with E-MDS. No statistical difference was found in IL-23 mRNA expression or plasma IL-22, IL-17 levels among E-MDS, L-MDS and controls. Our data demonstrated that L-MDS cohort had increased frequencies of peripheral Th22 cells and higher mRNA expression levels of IL-6 and TNF-α, indicating that Th22 cells along with Th17 cells or not are involved in the dynamic immune responses of MDS.
登录
查看更多内容
影响因子：
64.5
作者：
Ivanov, Ivaylo I.;McKenzie, Brent S.;Littman, Dan R.
通讯作者：
Littman, Dan R.
影响因子：
20.3
作者：
Kondo, Asaka;Yamashita, Taishi;Ogata, Kiyoyuki
通讯作者：
Ogata, Kiyoyuki
影响因子：
20.3
作者：
Parker, JE;Mufti, GJ;Pagliuca, A
通讯作者：
Pagliuca, A
影响因子：
30.5
作者：
Duhen, Thomas;Geiger, Rebekka;Sallusto, Federica
通讯作者：
Sallusto, Federica
影响因子：
4.4
作者：
Dhiman, Rohan;Indramohan, Mohanalaxmi;Vankayalapati, Ramakrishna
通讯作者：
Vankayalapati, Ramakrishna